The goal of this project is to determine (i) how the respiratory neural network generates the swallow-breathing pattern during the pharyngeal phase of swallowing, (ii) iterative computational modeling and simulation analysis testing model-based predictions on the recruitment, reconfiguration and output pattern of the neural elements that mediate the swallow-breathing pattern and (iii) mechanisms for induced load compensation modulation and coordination of neural elements that control breathing and swallow. Our central hypothesis is that induced reflex pharyngeal swallow generates a specific swallow-breathing pattern by swallow central pattern generator (sCPG) reconfiguration of the respiratory central pattern generator (rCPG). It is further hypothesized that current breathing-related treatments for dysphagia are effective by compensation induced reconfiguration and activation of convergent neural elements in sCPG and rCPGs that control upper airway, pharyngeal and respiratory muscles. The sCPG must reconfigure the respiratory neural network because many of the muscles used for control of the pharynx and larynx during breathing are also used during swallow. We propose that the swallow-respiratory pattern is controlled by neuronal assemblies dynamically organized into regulatory elements required for the expression of airway defensive behaviors. These behavioral control assemblies for swallow are composed of recruited sCPG neurons that exhibit recruited connectivity with the rCPG and reconfigure the respiratory neural network to generate the swallow-breathing pattern. Our overall approach will be to simultaneously record multiple brainstem neurons using our well established cat model of airway defensive reflexes. Our custom network modeling and simulation analysis will enable us to determine and predict the recruitment, reconfiguration and output pattern of the sCPG and rCPG neural elements mediating the swallow breathing pattern as well as load compensation modulation of swallow. There are 3 Specific Aims. In Specific Aim 1, multiple neurons in the dorsal and ventral swallow and respiratory groups will be recorded simultaneously during breathing and swallow. Advanced spike train analysis and metrics will be used to determine cooperative discharge patterns among these neurons specific to the rCPG, sCPG and swallow control of breathing. In Specific Aim 2, we will revise and test our model of the swallow network. We will incorporate inferred functional interactions among specific brainstem swallow and respiratory neuronal populations identified from analyses of spike trains simultaneously recorded with multiple electrode arrays. In Specific Aim 3, we will use our neural network model simulation to predict the effect of increased respiratory loads on recruited and reconfigured neural elements generating the swallow-breathing pattern. This research project will provide new and directly relevant insights into the control and coordination of swallow breathing pattern, predictions necessary to understand these control systems and potential neural mechanisms that may rehabilitate the failure of these control systems in disease. PUBLIC HEALTH RELEVANCE: Dysphagia commonly results in penetration and aspiration of bolus material into the lower airways, thereby contributing to a major cause of morbidity and mortality after a stroke or with neuromuscular disease. This project will increase our understanding of the basic neural mechanisms that integrate swallow and breathing and the respiratory-related neural mechanisms of dysphagia rehabilitation.